A review of the usefulness of clinical supervisor reports when writing educational supervisor reports.

In GP training, educational supervisors are responsible for collating evidence of a trainee's performance and progress to allow them to progress to the next stage of training. In hospital posts, they rely upon a clinical supervisor's report to help assess progress. Clinical supervisors are clinicians from various specialties who may not have an in-depth knowledge of the GP training programme, and anecdotally, our impression was that clinical supervisor reports were impersonal and not helpful in assessing a trainee's performance. We set out to evaluate the usefulness of a clinical supervisor's report in the context of completing and educational supervisor report for trainees in hospital posts. We reviewed clinical supervisor and educational supervisor reports for a cohort of 30 trainees in the Wessex Deanery, and conducted a questionnaire for their educational supervisors. All educational supervisors valued the clinical supervisor reports in completing their report, those with personal comments being the most useful. The majority of reports had a mixture of personal and generic comments. Overall, clinical supervisor reports provide additional information to evaluate performance, and they should continue to be used. To improve their use further, guidance can be given to clinical supervisors about the value of personal comments for trainees.

Peptidomics of enteroendocrine cells and characterisation of potential effects of a novel preprogastrin derived-peptide on glucose tolerance in lean mice.

OBJECTIVES: To analyse the peptidomics of mouse enteroendocrine cells (EECs) and human gastrointestinal (GI) tissue and identify novel gut derived peptides. METHODS: High resolution nano-flow liquid chromatography mass spectrometry (LC-MS/MS) was performed on (i) flow-cytometry purified NeuroD1 positive cells from mouse and homogenised human intestinal biopsies, (ii) supernatants from primary murine intestinal cultures, (iii) intestinal homogenates from mice fed high fat diet. Candidate bioactive peptides were selected on the basis of species conservation, high expression/biosynthesis in EECs and evidence of regulated secretionin vitro. Candidate novel gut-derived peptides were chronically administered to mice to assess effects on food intake and glucose tolerance. RESULTS: A large number of peptide fragments were identified from human and mouse, including known full-length gut hormones and enzymatic degradation products. EEC-specific peptides were largely from vesicular proteins, particularly prohormones, granins and processing enzymes, of which several exhibited regulated secretion in vitro. No regulated peptides were identified from previously unknown genes. High fat feeding particularly affected the distal colon, resulting in reduced peptide levels from GCG, PYY and INSL5. Of the two candidate novel peptides tested in vivo, a peptide from Chromogranin A (ChgA 435-462a) had no measurable effect, but a progastrin-derived peptide (Gast p59-79), modestly improved glucose tolerance in lean mice. CONCLUSION: LC-MS/MS peptidomic analysis of murine EECs and human GI tissue identified the spectrum of peptides produced by EECs, including a potential novel gut hormone, Gast p59-79, with minor effects on glucose tolerance.

Controlling the bioactivity of a peptide hormone in vivo by reversible self-assembly.

The use of peptides as therapeutic agents is undergoing a renaissance with the expectation of new drugs with enhanced levels of efficacy and safety. Their clinical potential will be only fully realised once their physicochemical and pharmacokinetic properties have been precisely controlled. Here we demonstrate a reversible peptide self-assembly strategy to control and prolong the bioactivity of a native peptide hormone in vivo. We show that oxyntomodulin, a peptide with potential to treat obesity and diabetes, self-assembles into a stable nanofibril formulation which subsequently dissociates to release active peptide and produces a pharmacological effect in vivo. The subcutaneous administration of the nanofibrils in rats results in greatly prolonged exposure, with a constant oxyntomodulin bioactivity detectable in serum for at least 5 days as compared to free oxyntomodulin which is undetectable after only 4 h. Such an approach is simple, cost-efficient and generic in addressing the limitations of peptide therapeutics.